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Aging and Disease    2014, Vol. 5 Issue (2) : 137-149     DOI: 10.14336/AD.2014.0500137
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Sepsis-induced Cardiac Mitochondrial Damage and Potential Therapeutic Interventions in the Elderly
Qun S. Zang, Steven E. Wolf, Joseph P. Minei
Departments of Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA
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Abstract  

The incidence of sepsis and its attendant mortality risk are significantly increased with aging. Thus, severe sepsis in the elderly is likely to become an emerging concern in critical care units. Cardiac dysfunction is an important component of multi-organ failure after sepsis. In our laboratory, utilizing a pneumonia-related sepsis animal model, our research has been focused on the mechanisms underlying sepsis-induced cardiac failure. In this review, based on findings from others and ours, we discussed age-dependent decay in mitochondria and the role of mitochondrial reactive oxygen species (mtROS) in sepsis-induced cardiac inflammation and autophagy. Our recent discovery of a potential signal transduction pathway that triggers myocardial mitochondrial damage is also discussed. Because of the significance of mitochondria damage in the aging process and in sepsis pathogenesis, we hypothesize that specific enhancing mitochondrial antioxidant defense by mitochondria-targeted antioxidants (MTAs) may provide important therapeutic potential in treating elder sepsis patients. In this review, we summarized the categories of currently published MTA molecules and the results of preclinical evaluation of MTAs in sepsis and aging models.

Keywords mitochondria      sepsis      cardiac function      inflammation      autophagy      mitochondria-targeted antioxidants     
Corresponding Authors: Qun S. Zang   
Issue Date: 10 March 2014
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Qun S. Zang
Steven E. Wolf
Joseph P. Minei
Cite this article:   
Qun S. Zang,Steven E. Wolf,Joseph P. Minei. Sepsis-induced Cardiac Mitochondrial Damage and Potential Therapeutic Interventions in the Elderly[J]. Aging and Disease, 2014, 5(2): 137-149.
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http://www.aginganddisease.org/EN/10.14336/AD.2014.0500137     OR     http://www.aginganddisease.org/EN/Y2014/V5/I2/137
[1] Angus DC, Pereira CA, Silva E(2006). Epidemiology of severe sepsis around the world. Endocr Metab Immune Disord Drug Targets, 6:207-212
[2] Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA(1992). Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest, 101:1644-1655
[3] Moss M, Martin GS(2004). A global perspective on the epidemiology of sepsis. Intensive care medicine, 30:527-529
[4] Levy MM, Dellinger RP, Townsend SR, Linde-Zwirble WT, Marshall JC, Bion J The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med, 38:367-374
[5] O’Brien JMJr, Ali NA, Aberegg SK, Abraham E(2007). Sepsis. Am J Med, 120:1012-1022
[6] Marik PE(2006). Management of the critically ill geriatric patient. Critical care medicine, 34:S176-182
[7] Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR(2001). Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Critical care medicine, 29:1303-1310
[8] Martin GS, Mannino DM, Moss M(2006). The effect of age on the development and outcome of adult sepsis. Critical care medicine, 34:15-21
[9] Nasa P, Juneja D, Singh O, Dang R, Arora V(2012). Severe sepsis and its impact on outcome in elderly and very elderly patients admitted in intensive care unit. Journal of intensive care medicine, 27:179-183
[10] Iwashyna TJ, Ely EW, Smith DM, Langa KM(2010). Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA : the journal of the American Medical Association, 304:1787-1794
[11] Franceschi C, Bonafe M, Valensin S(2000). Human immunosenescence: the prevailing of innate immunity, the failing of clonotypic immunity, and the filling of immunological space. Vaccine, 18:1717-1720
[12] Miller RA(2000). Effect of aging on T lymphocyte activation. Vaccine, 18:1654-1660
[13] Weksler ME(2000). Changes in the B-cell repertoire with age. Vaccine, 18:1624-1628
[14] Grubeck-Loebenstein B, Wick G(2002). The aging of the immune system. Advances in immunology, 80:243-284
[15] Plackett TP, Boehmer ED, Faunce DE, Kovacs EJ(2004). Aging and innate immune cells. Journal of leukocyte biology, 76:291-299
[16] Sanchez M, Lindroth K, Sverremark E, Gonzalez Fernandez A, Fernandez C(2001). The response in old mice: positive and negative immune memory after priming in early age. International immunology, 13:1213-1221
[17] Lebecque S(2000). Antigen receptors and dendritic cells. Vaccine, 18:1603-1605
[18] Herrero C, Marques L, Lloberas J, Celada A(2001). IFN-gamma-dependent transcription of MHC class II IA is impaired in macrophages from aged mice. The Journal of clinical investigation, 107:485-493
[19] Gabriel P, Cakman I, Rink L(2002). Overproduction of monokines by leukocytes after stimulation with lipopolysaccharide in the elderly. Experimental gerontology, 37:235-247
[20] Bruunsgaard H, Skinhoj P, Qvist J, Pedersen BK(1999). Elderly humans show prolonged in vivo inflammatory activity during pneumococcal infections. The Journal of infectious diseases, 180:551-554
[21] Jensen GL, McGee M, Binkley J(2001). Nutrition in the elderly. Gastroenterology clinics of North America, 30:313-334
[22] Chernow B(1999). Variables affecting outcome in critically ill patients. Chest, 115:71S-76S
[23] Stump TE, Callahan CM, Hendrie HC(2001). Cognitive impairment and mortality in older primary care patients. Journal of the American Geriatrics Society, 49:934-940
[24] Harman D(1956). Aging: a theory based on free radical and radiation chemistry. J Gerontol, 11:298-300
[25] Harrison R(2002). Structure and function of xanthine oxidoreductase: where are we now?. Free radical biology & medicine, 33:774-797
[26] Bedard K, Krause KH(2007). The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiological reviews, 87:245-313
[27] Schrader M, Fahimi HD(2006). Peroxisomes and oxidative stress. Biochimica et biophysica acta, 1763:1755-1766
[28] Barja G(1998). Mitochondrial free radical production and aging in mammals and birds. Annals of the New York Academy of Sciences, 854:224-238
[29] Antunes F, Han D, Cadenas E(2002). Relative contributions of heart mitochondria glutathione peroxidase and catalase to H(2)O(2) detoxification in in vivo conditions. Free radical biology & medicine, 33:1260-1267
[30] Melov S, Coskun P, Patel M, Tuinstra R, Cottrell B, Jun AS(1999). Mitochondrial disease in superoxide dismutase 2 mutant mice. Proceedings of the National Academy of Sciences of the United States of America, 96:846-851
[31] Radi R, Turrens JF, Chang LY, Bush KM, Crapo JD, Freeman BA(1991). Detection of catalase in rat heart mitochondria. The Journal of biological chemistry, 266:22028-22034
[32] Beal MF(2002). Oxidatively modified proteins in aging and disease. Free radical biology & medicine, 32:797-803
[33] Croteau DL, Bohr VA(1997). Repair of oxidative damage to nuclear and mitochondrial DNA in mammalian cells. The Journal of biological chemistry, 272:25409-25412
[34] Harman D(1972). Free radical theory of aging: dietary implications. The American journal of clinical nutrition, 25:839-843
[35] Unlu ES, Koc A(2007). Effects of deleting mitochondrial antioxidant genes on life span. Annals of the New York Academy of Sciences, 1100:505-509
[36] Melov S, Ravenscroft J, Malik S, Gill MS, Walker DW, Clayton PE(2000). Extension of life-span with superoxide dismutase/catalase mimetics. Science, 289:1567-1569
[37] Lee HY, Choi CS, Birkenfeld AL, Alves TC, Jornayvaz FR, Jurczak MJ(2010). Targeted expression of catalase to mitochondria prevents age-associated reductions in mitochondrial function and insulin resistance. Cell metabolism, 12:668-674
[38] Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M(2005). Extension of murine life span by overexpression of catalase targeted to mitochondria. Science, 308:1909-1911
[39] Perez VI, Van Remmen H, Bokov A, Epstein CJ, Vijg J, Richardson A(2009). The overexpression of major antioxidant enzymes does not extend the lifespan of mice. Aging cell, 8:73-75
[40] Dolara P, Bigagli E, Collins A(2012). Antioxidant vitamins and mineral supplementation, life span expansion and cancer incidence: a critical commentary. European journal of nutrition, 51:769-781
[41] Kayar SR, Banchero N(1987). Volume density and distribution of mitochondria in myocardial growth and hypertrophy. Respir Physiol, 70:275-286
[42] Judge S, Jang YM, Smith A, Hagen T, Leeuwenburgh C(2005). Age-associated increases in oxidative stress and antioxidant enzyme activities in cardiac interfibrillar mitochondria: implications for the mitochondrial theory of aging. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 19:419-421
[43] Dai DF, Rabinovitch PS, Ungvari Z(2012). Mitochondria and cardiovascular aging. Circulation research, 110:1109-1124
[44] Dai DF, Hsieh EJ, Liu Y, Chen T, Beyer RP, Chin MT(2012). Mitochondrial proteome remodelling in pressure overload-induced heart failure: the role of mitochondrial oxidative stress. Cardiovascular research, 93:79-88
[45] Dai DF, Johnson SC, Villarin JJ, Chin MT, Nieves-Cintron M, Chen T(2011). Mitochondrial oxidative stress mediates angiotensin II-induced cardiac hypertrophy and Galphaq overexpression-induced heart failure. Circulation research, 108:837-846
[46] Dai DF, Santana LF, Vermulst M, Tomazela DM, Emond MJ, MacCoss MJ(2009). Overexpression of catalase targeted to mitochondria attenuates murine cardiac aging. Circulation, 119:2789-2797
[47] Shen X, Zheng S, Metreveli NS, Epstein PN(2006). Protection of cardiac mitochondria by overexpression of MnSOD reduces diabetic cardiomyopathy. Diabetes, 55:798-805
[48] Loch T, Vakhrusheva O, Piotrowska I, Ziolkowski W, Ebelt H, Braun T(2009). Different extent of cardiac malfunction and resistance to oxidative stress in heterozygous and homozygous manganese-dependent superoxide dismutase-mutant mice. Cardiovascular research, 82:448-457
[49] Court O, Kumar A, Parrillo JE(2002). Clinical review: Myocardial depression in sepsis and septic shock. Crit Care, 6:500-508
[50] Zanotti-Cavazzoni SL, Hollenberg SM(2009). Cardiac dysfunction in severe sepsis and septic shock. Curr Opin Crit Care, 15:392-397
[51] Rudiger A, Singer M(2007). Mechanisms of sepsis-induced cardiac dysfunction. Critical care medicine, 35:1599-1608
[52] Blanco J, Muriel-Bombin A, Sagredo V, Taboada F, Gandia F, Tamayo L(2008). Incidence, organ dysfunction and mortality in severe sepsis: a Spanish multicentre study. Crit Care, 12:R158
[53] Parrillo JE, Parker MM, Natanson C, Suffredini AF, Danner RL, Cunnion RE(1990). Septic shock in humans. Advances in the understanding of pathogenesis, cardiovascular dysfunction, and therapy. Annals of internal medicine, 113:227-242
[54] Brealey D, Brand M, Hargreaves I, Heales S, Land J, Smolenski R(2002). Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet, 360:219-223
[55] Cairns CB, Moore FA, Haenel JB, Gallea BL, Ortner JP, Rose SJ(1997). Evidence for early supply independent mitochondrial dysfunction in patients developing multiple organ failure after trauma. The Journal of trauma, 42:532-536
[56] Watts JA, Kline JA, Thornton LR, Grattan RM, Brar SS(2004). Metabolic dysfunction and depletion of mitochondria in hearts of septic rats. Journal of molecular and cellular cardiology, 36:141-150
[57] Levy RJ(2007). Mitochondrial dysfunction, bioenergetic impairment, and metabolic down-regulation in sepsis. Shock, 28:24-28
[58] Callahan LA, Supinski GS(2007). Diaphragm and cardiac mitochondrial creatine kinases are impaired in sepsis. J Appl Physiol, 102:44-53
[59] Akira S, Uematsu S, Takeuchi O(2006). Pathogen recognition and innate immunity. Cell, 124:783-801
[60] Matzinger P(1994). Tolerance, danger, and the extended family. Annu Rev Immunol, 12:991-1045
[61] Codina R, Vanasse A, Kelekar A, Vezys V, Jemmerson R(2010). Cytochrome c-induced lymphocyte death from the outside in: inhibition by serum leucine-rich alpha-2-glycoprotein-1. Apoptosis, 15:139-152
[62] Creagh EM, O’Neill LA(2006). TLRs, NLRs and RLRs: a trinity of pathogen sensors that co-operate in innate immunity. Trends Immunol, 27:352-357
[63] Uematsu S, Akira S(2006). Toll-like receptors and innate immunity. J Mol Med, 84:712-725
[64] Geijtenbeek TB, Gringhuis SI(2009). Signalling through C-type lectin receptors: shaping immune responses. Nature reviews. Immunology, 9:465-479
[65] Osorio F, Reis e Sousa C(2011). Myeloid C-type lectin receptors in pathogen recognition and host defense. Immunity, 34:651-664
[66] Orange JS, Geha RS(2003). Finding NEMO: genetic disorders of NF-[kappa]B activation. J Clin Invest, 112:983-985
[67] Israel A(2000). The IKK complex: an integrator of all signals that activate NF-kappaB?. Trends Cell Biol, 10:129-133
[68] Cinel I, Opal SM(2009). Molecular biology of inflammation and sepsis: a primer. Critical care medicine, 37:291-304
[69] Martinon F, Mayor A, Tschopp J(2009). The inflammasomes: guardians of the body. Annu Rev Immunol, 27:229-265
[70] Lee MS, Kim YJ(2007). Signaling pathways downstream of pattern-recognition receptors and their cross talk. Annu Rev Biochem, 76:447-480
[71] Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W(2010). Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature, 464:104-107
[72] Carp H(1982). Mitochondrial N-formylmethionyl proteins as chemoattractants for neutrophils. J Exp Med, 155:264-275
[73] Czapiga M, Gao JL, Kirk A, Lekstrom-Himes J(2005). Human platelets exhibit chemotaxis using functional N-formyl peptide receptors. Exp Hematol, 33:73-84
[74] Bjorkman L, Karlsson J, Karlsson A, Rabiet MJ, Boulay F, Fu H(2008). Serum amyloid A mediates human neutrophil production of reactive oxygen species through a receptor independent of formyl peptide receptor like-1. Journal of leukocyte biology, 83:245-253
[75] Ghiringhelli F, Apetoh L, Tesniere A, Aymeric L, Ma Y, Ortiz C(2009). Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. Nature medicine, 15:1170-1178
[76] Iyer SS, Pulskens WP, Sadler JJ, Butter LM, Teske GJ, Ulland TK(2009). Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome. Proceedings of the National Academy of Sciences of the United States of America, 106:20388-20393
[77] Pullerits R, Bokarewa M, Jonsson IM, Verdrengh M, Tarkowski A(2005). Extracellular cytochrome c, a mitochondrial apoptosis-related protein, induces arthritis. Rheumatology (Oxford)44:32-39
[78] Zhang Q, Itagaki K, Hauser CJ MITOCHONDRIAL DNA IS RELEASED BY SHOCK AND ACTIVATES NEUTROPHILS VIA p38 MAP-KINASE. Shock
[79] Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature, 464:104-107
[80] Zhou R, Yazdi AS, Menu P, Tschopp J(2011). A role for mitochondria in NLRP3 inflammasome activation. Nature, 469:221-225
[81] Seth RB, Sun L, Ea CK, Chen ZJ(2005). Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell, 122:669-682
[82] Tsutsui H, Kinugawa S, Matsushima S(2008). Oxidative stress and mitochondrial DNA damage in heart failure. Circ J, 72(Suppl A):A31-37
[83] Ballinger SW(2005). Mitochondrial dysfunction in cardiovascular disease. Free radical biology & medicine, 38:1278-1295
[84] Boyd JH, Mathur S, Wang Y, Bateman RM, Walley KR(2006). Toll-like receptor stimulation in cardiomyoctes decreases contractility and initiates an NF-kappaB dependent inflammatory response. Cardiovasc Res, 72:384-393
[85] Knuefermann P, Schwederski M, Velten M, Krings P, Ehrentraut H, Rudiger M(2008). Bacterial DNA induces myocardial inflammation and reduces cardiomyocyte contractility: role of toll-like receptor 9. Cardiovasc Res, 78:26-35
[86] Yin Y, Yan Y, Jiang X, Mai J, Chen NC, Wang H(2009). Inflammasomes are differentially expressed in cardiovascular and other tissues. Int J Immunopathol Pharmacol, 22:311-322
[87] Neviere R, Fauvel H, Chopin C, Formstecher P, Marchetti P(2001). Caspase inhibition prevents cardiac dysfunction and heart apoptosis in a rat model of sepsis. Am J Respir Crit Care Med, 163:218-225
[88] Schmidt C, Kurt B, Hocherl K, Bucher M(2009). Inhibition of NF-kappaB activity prevents downregulation of alpha1-adrenergic receptors and circulatory failure during CLP-induced sepsis. Shock, 32:239-246
[89] Zang QS, Sadek H, Maass DL, Martinez B, Ma L, Kilgore JA(2012). Specific inhibition of mitochondrial oxidative stress suppresses inflammation and improves cardiac function in a rat pneumonia-related sepsis model. American journal of physiology. Heart and circulatory physiology, 302:H1847-1859
[90] Oka T, Hikoso S, Yamaguchi O, Taneike M, Takeda T, Tamai T(2012). Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure. Nature, 485:251-255
[91] Greenhalgh DG, Saffle JR, Holmes JHt, Gamelli RL, Palmieri TL, Horton JW(2007). American Burn Association consensus conference to define sepsis and infection in burns. J Burn Care Res, 28:776-790
[92] Wang L, Quan J, Johnston WE, Maass DL, Horton JW, Thomas JA(2010). Age-dependent differences of interleukin-6 activity in cardiac function after burn complicated by sepsis. Burns, 36:232-238
[93] Sheeran PW, Maass DL, White DJ, Turbeville TD, Giroir BP, Horton JW(1998). Aspiration pneumonia-induced sepsis increases cardiac dysfunction after burn trauma. The Journal of surgical research, 76:192-199
[94] White J, Thomas J, Maass DL, Horton JW(2003). Cardiac effects of burn injury complicated by aspiration pneumonia-induced sepsis. American journal of physiology. Heart and circulatory physiology, 285:H47-58
[95] Tao W, Maass DL, Johnston WE, Horton JW(2005). Murine in vivo myocardial contractile dysfunction after burn injury is exacerbated by pneumonia sepsis. Shock, 24:495-499
[96] Zang Q, Maass DL, Tsai SJ, Horton JW(2007). Cardiac mitochondrial damage and inflammation responses in sepsis. Surg Infect (Larchmt)8:41-54
[97] Reynolds CM, Suliman HB, Hollingsworth JW, Welty-Wolf KE, Carraway MS, Piantadosi CA(2009). Nitric oxide synthase-2 induction optimizes cardiac mitochondrial biogenesis after endotoxemia. Free radical biology & medicine, 46:564-572
[98] Fauconnier J, Meli AC, Thireau J, Roberge S, Shan J, Sassi Y Ryanodine receptor leak mediated by caspase-8 activation leads to left ventricular injury after myocardial ischemia-reperfusion. Proceedings of the National Academy of Sciences of the United States of America
[99] Mizushima N, Levine B(2010). Autophagy in mammalian development and differentiation. Nat Cell Biol, 12:823-830
[100] Yamamoto S, Sawada K, Shimomura H, Kawamura K, James TN(2000). On the nature of cell death during remodeling of hypertrophied human myocardium. Journal of molecular and cellular cardiology, 32:161-175
[101] Yan L, Vatner DE, Kim SJ, Ge H, Masurekar M, Massover WH(2005). Autophagy in chronically ischemic myocardium. Proceedings of the National Academy of Sciences of the United States of America, 102:13807-13812
[102] Matsui Y, Takagi H, Qu X, Abdellatif M, Sakoda H, Asano T(2007). Distinct roles of autophagy in the heart during ischemia and reperfusion: roles of AMP-activated protein kinase and Beclin 1 in mediating autophagy. Circulation research, 100:914-922
[103] Zhu H, Rothermel BA, Hill JA(2009). Autophagy in load-induced heart disease. Methods Enzymol, 453:343-363
[104] Zhu H, Tannous P, Johnstone JL, Kong Y, Shelton JM, Richardson JA(2007). Cardiac autophagy is a maladaptive response to hemodynamic stress. The Journal of clinical investigation, 117:1782-1793
[105] Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H(1999). Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature, 402:672-676
[106] Kroemer G, Marino G, Levine B(2010). Autophagy and the integrated stress response. Mol Cell, 40:280-293
[107] Levine B, Kroemer G(2008). Autophagy in the pathogenesis of disease. Cell, 132:27-42
[108] Tannous P, Zhu H, Johnstone JL, Shelton JM, Rajasekaran NS, Benjamin IJ(2008). Autophagy is an adaptive response in desmin-related cardiomyopathy. Proceedings of the National Academy of Sciences of the United States of America, 105:9745-9750
[109] Hill JA(2011). Autophagy in cardiac plasticity and disease. Pediatr Cardiol, 32:282-289
[110] Ferdous A, Battiprolu PK, Ni YG, Rothermel BA, Hill JA(2010). FoxO, autophagy, and cardiac remodeling. Journal of cardiovascular translational research, 3:355-364
[111] Xie M, Morales CR, Lavandero S, Hill JA(2011). Tuning flux: autophagy as a target of heart disease therapy. Curr Opin Cardiol, 26:216-222
[112] Inuzuka Y, Okuda J, Kawashima T, Kato T, Niizuma S, Tamaki Y(2009). Suppression of phosphoinositide 3-kinase prevents cardiac aging in mice. Circulation, 120:1695-1703
[113] Taneike M, Yamaguchi O, Nakai A, Hikoso S, Takeda T, Mizote I(2010). Inhibition of autophagy in the heart induces age-related cardiomyopathy. Autophagy, 6:600-606
[114] Sachs HG, Colgan JA, Lazarus ML(1977). Ultrastructure of the aging myocardium: a morphometric approach. The American journal of anatomy, 150:63-71
[115] Coleman R, Silbermann M, Gershon D, Reznick AZ(1987). Giant mitochondria in the myocardium of aging and endurance-trained mice. Gerontology, 33:34-39
[116] Levine B, Mizushima N, Virgin HW(2011). Autophagy in immunity and inflammation. Nature, 469:323-335
[117] Cuervo AM, Dice JF(2000). When lysosomes get old. Experimental gerontology, 35:119-131
[118] Nakano M, Oenzil F, Mizuno T, Gotoh S(1995). Age-related changes in the lipofuscin accumulation of brain and heart. Gerontology, 41(Suppl 2):69-79
[119] Brunk UT, Terman A(2002). Lipofuscin: mechanisms of age-related accumulation and influence on cell function. Free radical biology & medicine, 33:611-619
[120] Mofarrahi M, Sigala I, Guo Y, Godin R, Davis EC, Petrof B(2012). Autophagy and skeletal muscles in sepsis. PloS one, 7:e47265
[121] Hsiao HW, Tsai KL, Wang LF, Chen YH, Chiang PC, Chuang SM(2012). The decline of autophagy contributes to proximal tubular dysfunction during sepsis. Shock, 37:289-296
[122] Chien WS, Chen YH, Chiang PC, Hsiao HW, Chuang SM, Lue SI(2011). Suppression of autophagy in rat liver at late stage of polymicrobial sepsis. Shock, 35:506-511
[123] Watanabe E, Muenzer JT, Hawkins WG, Davis CG, Dixon DJ, McDunn JE(2009). Sepsis induces extensive autophagic vacuolization in hepatocytes: a clinical and laboratory-based study. Laboratory investigation; a journal of technical methods and pathology, 89:549-561
[124] Li L, Chen Y, Gibson SB(2013). Starvation-induced autophagy is regulated by mitochondrial reactive oxygen species leading to AMPK activation. Cellular signalling, 25:50-65
[125] Lee J, Giordano S, Zhang J(2012). Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling. The Biochemical journal, 441:523-540
[126] Morales CR, Pedrozo Z, Lavandero S, Hill JA(2013). Oxidative Stress and Autophagy in Cardiovascular Homeostasis. Antioxidants & redox signaling
[127] Hsieh CH, Pai PY, Hsueh HW, Yuan SS, Hsieh YC(2011). Complete induction of autophagy is essential for cardioprotection in sepsis. Annals of surgery, 253:1190-1200
[128] Yuan H, Perry CN, Huang C, Iwai-Kanai E, Carreira RS, Glembotski CC(2009). LPS-induced autophagy is mediated by oxidative signaling in cardiomyocytes and is associated with cytoprotection. American journal of physiology. Heart and circulatory physiology, 296:H470-479
[129] Turdi S, Han X, Huff AF, Roe ND, Hu N, Gao F(2012). Cardiac-specific overexpression of catalase attenuates lipopolysaccharide-induced myocardial contractile dysfunction: role of autophagy. Free radical biology & medicine, 53:1327-1338
[130] Zang QS, Martinez B, Yao X, Maass DL, Ma L, Wolf SE(2012). Sepsis-Induced Cardiac Mitochondrial Dysfunction Involves Altered Mitochondrial-Localization of Tyrosine Kinase Src and Tyrosine Phosphatase SHP2. PloS one, 7:e43424
[131] Tibaldi E, Brunati AM, Massimino ML, Stringaro A, Colone M, Agostinelli E(2008). Src-Tyrosine kinases are major agents in mitochondrial tyrosine phosphorylation. J Cell Biochem, 104:840-849
[132] Arachiche A, Augereau O, Decossas M, Pertuiset C, Gontier E, Letellier T(2008). Localization of PTP-1B, SHP-2, and Src exclusively in rat brain mitochondria and functional consequences. The Journal of biological chemistry, 283:24406-24411
[133] Budas GR, Churchill EN, Disatnik MH, Sun L, Mochly-Rosen D(2010). Mitochondrial import of PKCepsilon is mediated by HSP90: a role in cardioprotection from ischaemia and reperfusion injury. Cardiovascular research, 88:83-92
[134] Guo J, Cong L, Rybin VO, Gertsberg Z, Steinberg SF(2010). Protein kinase C-{delta} regulates the subcellular localization of Shc in H2O2-treated cardiomyocytes. American journal of physiology. Cell physiology, 299:C770-778
[135] Alonso M, Melani M, Converso D, Jaitovich A, Paz C, Carreras MC(2004). Mitochondrial extracellular signal-regulated kinases 1/2 (ERK1/2) are modulated during brain development. J Neurochem, 89:248-256
[136] Monick MM, Powers LS, Barrett CW, Hinde S, Ashare A, Groskreutz DJ(2008). Constitutive ERK MAPK activity regulates macrophage ATP production and mitochondrial integrity. J Immunol, 180:7485-7496
[137] Miyazaki T, Neff L, Tanaka S, Horne WC, Baron R(2003). Regulation of cytochrome c oxidase activity by c-Src in osteoclasts. J Cell Biol, 160:709-718
[138] Feng J, Lucchinetti E, Enkavi G, Wang Y, Gehrig P, Roschitzki B(2010). Tyrosine phosphorylation by Src within the cavity of the adenine nucleotide translocase 1 regulates ADP/ATP exchange in mitochondria. American journal of physiology. Cell physiology, 298:C740-748
[139] Lewandrowski U, Sickmann A, Cesaro L, Brunati AM, Toninello A, Salvi M(2008). Identification of new tyrosine phosphorylated proteins in rat brain mitochondria. FEBS Lett, 582:1104-1110
[140] Augereau O, Claverol S, Boudes N, Basurko MJ, Bonneu M, Rossignol R(2005). Identification of tyrosine-phosphorylated proteins of the mitochondrial oxidative phosphorylation machinery. Cell Mol Life Sci, 62:1478-1488
[141] Deng N, Zhang J, Zong C, Wang Y, Lu H, Yang P(2011). Phosphoproteome analysis reveals regulatory sites in major pathways of cardiac mitochondria. Mol Cell Proteomics, 10:M110 000117
[142] Schulenberg B, Aggeler R, Beechem JM, Capaldi RA, Patton WF(2003). Analysis of steady-state protein phosphorylation in mitochondria using a novel fluorescent phosphosensor dye. J Biol Chem, 278:27251-27255
[143] Chen R, Fearnley IM, Peak-Chew SY, Walker JE(2004). The phosphorylation of subunits of complex I from bovine heart mitochondria. The Journal of biological chemistry, 279:26036-26045
[144] Steenaart NA, Shore GC(1997). Mitochondrial cytochrome c oxidase subunit IV is phosphorylated by an endogenous kinase. FEBS Lett, 415:294-298
[145] Ko YH, Pan W, Inoue C, Pedersen PL(2002). Signal transduction to mitochondrial ATP synthase: evidence that PDGF-dependent phosphorylation of the delta-subunit occurs in several cell lines, involves tyrosine, and is modulated by lysophosphatidic acid. Mitochondrion, 1:339-348
[146] Salvi M, Morrice NA, Brunati AM, Toninello A(2007). Identification of the flavoprotein of succinate dehydrogenase and aconitase as in vitro mitochondrial substrates of Fgr tyrosine kinase. FEBS Lett, 581:5579-5585
[147] Jakob S, Altschmied J, Haendeler J(2009). “Shping 2” different cellular localizations - a potential new player in aging processes. Aging, 1:664-668
[148] Chen Q, Vazquez EJ, Moghaddas S, Hoppel CL, Lesnefsky EJ(2003). Production of reactive oxygen species by mitochondria: central role of complex III. The Journal of biological chemistry, 278:36027-36031
[149] Hebert-Chatelain E, Jose C, Gutierrez Cortes N, Dupuy JW, Rocher C, Dachary-Prigent J(2012). Preservation of NADH ubiquinone-oxidoreductase activity by Src kinase-mediated phosphorylation of NDUFB10. Biochimica et biophysica acta, 1817:718-725
[150] Hebert Chatelain E, Dupuy JW, Letellier T, Dachary-Prigent J(2011). Functional impact of PTP1B-mediated Src regulation on oxidative phosphorylation in rat brain mitochondria. Cell Mol Life Sci, 68:2603-2613
[151] Reznick RM, Shulman GI(2006). The role of AMP-activated protein kinase in mitochondrial biogenesis. The Journal of physiology, 574:33-39
[152] Reznick RM, Zong H, Li J, Morino K, Moore IK, Yu HJ(2007). Aging-associated reductions in AMP-activated protein kinase activity and mitochondrial biogenesis. Cell metabolism, 5:151-156
[153] Nemoto S, Combs CA, French S, Ahn BH, Fergusson MM, Balaban RS(2006). The mammalian longevity-associated gene product p66shc regulates mitochondrial metabolism. The Journal of biological chemistry, 281:10555-10560
[154] Cosentino F, Francia P, Camici GG, Pelicci PG, Luscher TF, Volpe M(2008). Final common molecular pathways of aging and cardiovascular disease: role of the p66Shc protein. Arteriosclerosis, thrombosis, and vascular biology, 28:622-628
[155] Rinaldi S, Landucci F, De Gaudio AR(2009). Antioxidant therapy in critically septic patients. Curr Drug Targets, 10:872-880
[156] Andrades ME, Ritter C, Dal-Pizzol F(2009). The role of free radicals in sepsis development. Front Biosci (Elite Ed)1:277-287
[157] Ritter C, Andrades ME, Reinke A, Menna-Barreto S, Moreira JC, Dal-Pizzol F(2004). Treatment with N-acetylcysteine plus deferoxamine protects rats against oxidative stress and improves survival in sepsis. Critical care medicine, 32:342-349
[158] Long CL, Maull KI, Krishnan RS, Laws HL, Geiger JW, Borghesi L(2003). Ascorbic acid dynamics in the seriously ill and injured. The Journal of surgical research, 109:144-148
[159] Angstwurm MW, Engelmann L, Zimmermann T, Lehmann C, Spes CH, Abel P(2007). Selenium in Intensive Care (SIC): results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock. Crit Care Med, 35:118-126
[160] Forceville X, Laviolle B, Annane D, Vitoux D, Bleichner G, Korach JM(2007). Effects of high doses of selenium, as sodium selenite, in septic shock: a placebo-controlled, randomized, double-blind, phase II study. Crit Care, 11:R73
[161] Berger MM, Chiolero RL(2007). Antioxidant supplementation in sepsis and systemic inflammatory response syndrome. Critical care medicine, 35:S584-590
[162] Lovat R, Preiser JC(2003). Antioxidant therapy in intensive care. Curr Opin Crit Care, 9:266-270
[163] Adlam VJ, Harrison JC, Porteous CM, James AM, Smith RA, Murphy MP(2005). Targeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion injury. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 19:1088-1095
[164] Szeto HH(2006). Cell-permeable, mitochondrial-targeted, peptide antioxidants. AAPS J, 8:E277-283
[165] Amstislavskaya TG, Maslova LN, Gladkikh DV, Belousova II, Stefanova NA, Kolosova NG Effects of the mitochondria-targeted antioxidant SkQ1 on sexually motivated behavior in male rats. Pharmacol Biochem Behav
[166] Demianenko IA, Vasilieva TV, Domnina LV, Dugina VB, Egorov MV, Ivanova OY Novel mitochondria-targeted antioxidants, “Skulachev-ion” derivatives, accelerate dermal wound healing in animals. Biochemistry. Biokhimiia, 75:274-280
[167] Coulter CV, Kelso GF, Lin TK, Smith RA, Murphy MP(2000). Mitochondrially targeted antioxidants and thiol reagents. Free radical biology & medicine, 28:1547-1554
[168] Murphy MP, Smith RA(2007). Targeting antioxidants to mitochondria by conjugation to lipophilic cations. Annual review of pharmacology and toxicology, 47:629-656
[169] Smith RA, Porteous CM, Gane AM, Murphy MP(2003). Delivery of bioactive molecules to mitochondria in vivo. Proceedings of the National Academy of Sciences of the United States of America, 100:5407-5412
[170] Szeto HH(2008). Mitochondria-targeted cytoprotective peptides for ischemia-reperfusion injury. Antioxidants & redox signaling, 10:601-619
[171] Lowes DA, Wallace C, Murphy MP, Webster NR, Galley HF(2009). The mitochondria targeted antioxidant MitoQ protects against fluoroquinolone-induced oxidative stress and mitochondrial membrane damage in human Achilles tendon cells. Free radical research, 43:323-328
[172] Dhanasekaran A, Kotamraju S, Kalivendi SV, Matsunaga T, Shang T, Keszler A(2004). Supplementation of endothelial cells with mitochondria-targeted antioxidants inhibit peroxide-induced mitochondrial iron uptake, oxidative damage, and apoptosis. J Biol Chem, 279:37575-37587
[173] Dhanasekaran A, Kotamraju S, Karunakaran C, Kalivendi SV, Thomas S, Joseph J(2005). Mitochondria superoxide dismutase mimetic inhibits peroxide-induced oxidative damage and apoptosis: role of mitochondrial superoxide. Free Radic Biol Med, 39:567-583
[174] Jauslin ML, Meier T, Smith RA, Murphy MP(2003). Mitochondria-targeted antioxidants protect Friedreich Ataxia fibroblasts from endogenous oxidative stress more effectively than untargeted antioxidants. FASEB J, 17:1972-1974
[175] Gane EJ, Weilert F, Orr DW, Keogh GF, Gibson M, Lockhart MM(2010). The mitochondria-targeted anti-oxidant mitoquinone decreases liver damage in a phase II study of hepatitis C patients. Liver international : official journal of the International Association for the Study of the Liver, 30:1019-1026
[176] Smith RA, Murphy MP(2010). Animal and human studies with the mitochondria-targeted antioxidant MitoQ. Annals of the New York Academy of Sciences, 1201:96-103
[177] Ghosh A, Chandran K, Kalivendi SV, Joseph J, Antholine WE, Hillard CJ(2010). Neuroprotection by a mitochondria-targeted drug in a Parkinson’s disease model. Free radical biology & medicine, 49:1674-1684
[178] Manczak M, Mao P, Calkins MJ, Cornea A, Reddy AP, Murphy MP(2010). Mitochondria-targeted antioxidants protect against amyloid-beta toxicity in Alzheimer’s disease neurons. Journal of Alzheimer’s disease : JAD, 20 Suppl)2:S609-631
[179] Chandran K, Aggarwal D, Migrino RQ, Joseph J, McAllister D, Konorev EA(2009). Doxorubicin inactivates myocardial cytochrome c oxidase in rats: cardioprotection by Mito-Q. Biophys J, 96:1388-1398
[180] Dikalova AE, Bikineyeva AT, Budzyn K, Nazarewicz RR, McCann L, Lewis W Therapeutic targeting of mitochondrial superoxide in hypertension. Circulation research, 107:106-116
[181] Chacko BK, Reily C, Srivastava A, Johnson MS, Ye Y, Ulasova E(2010). Prevention of diabetic nephropathy in Ins2(+/)(AkitaJ) mice by the mitochondria-targeted therapy MitoQ. The Biochemical journal, 432:9-19
[182] Lowes DA, Thottakam BM, Webster NR, Murphy MP, Galley HF(2008). The mitochondria-targeted antioxidant MitoQ protects against organ damage in a lipopolysaccharide-peptidoglycan model of sepsis. Free radical biology & medicine, 45:1559-1565
[183] Supinski GS, Murphy MP, Callahan LA(2009). MitoQ administration prevents endotoxin-induced cardiac dysfunction. Am J Physiol Regul Integr Comp Physiol, 297:R1095-1102
[184] Antonenko YN, Avetisyan AV, Bakeeva LE, Chernyak BV, Chertkov VA, Domnina LV(2008). Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 1. Cationic plastoquinone derivatives: synthesis and in vitro studies. Biochemistry. Biokhimiia, 73:1273-1287
[185] Stefanova NA, Fursova A, Kolosova NG(2010). Behavioral effects induced by mitochondria-targeted antioxidant SkQ1 in Wistar and senescence-accelerated OXYS rats. Journal of Alzheimer’s disease : JAD, 21:479-491
[186] Shipounova IN, Svinareva DA, Petrova TV, Lyamzaev KG, Chernyak BV, Drize NI(2010). Reactive oxygen species produced in mitochondria are involved in age-dependent changes of hematopoietic and mesenchymal progenitor cells in mice. A study with the novel mitochondria-targeted antioxidant SkQ1. Mechanisms of ageing and development, 131:415-421
[187] Krementsova AV, Roshina NV, Tsybul’ko EA, Rybina OY, Symonenko AV, Pasyukova EG(2012). Reproducible effects of the mitochondria-targeted plastoquinone derivative SkQ1 on Drosophila melanogaster lifespan under different experimental scenarios. Biogerontology, 13:595-607
[188] Anisimov VN, Egorov MV, Krasilshchikova MS, Lyamzaev KG, Manskikh VN, Moshkin MP(2011). Effects of the mitochondria-targeted antioxidant SkQ1 on lifespan of rodents. Aging, 3:1110-1119
[189] Venkataraman R, Subramanian S, Kellum JA(2003). Clinical review: extracorporeal blood purification in severe sepsis. Crit Care, 7:139-145
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